The cell of origin topography is more obscure in osteosarcoma because the multitude of aberrations present in osteosarcoma genomes complicates most discovery studies [40–42], however, TP53 or RB1 loss-of-function [43, 44] or mutant gain-of-function [45, 46] in an osteoblastic like progenitor are accepted. Here, TP53 is linked to osteosarcoma.